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Is it safe? · Pregnancy Smart

Vaginal progesterone during pregnancy: short cervix

Assigned clinical reviewerMatt Stahl· PharmDDraft · pending clinical reviewUpdated

What does the evidence say about vaginal progesterone during pregnancy?

  1. Current ACOG guidance says vaginal progesterone may be considered when a singleton pregnancy has both a prior spontaneous early birth and a shortened cervix, but it should not be offered for that history alone when cervical length is not shortened. 1
  2. For people without a prior spontaneous early birth, a 2024 SMFM consult recommends vaginal progesterone in an asymptomatic singleton pregnancy with a transvaginal cervical length of 20 mm or less before 24 weeks, with shared decision-making at 21 to 25 mm. 2
  3. In a double-masked randomized trial of 458 asymptomatic singleton pregnancies with a 10 to 20 mm cervix, 90 mg vaginal progesterone gel lowered birth before 33 weeks from 16.1% with placebo to 8.9%. 3
  4. A post hoc meta-analysis of four trials and 1,308 singleton pregnancies with prior spontaneous preterm birth and cervical length above 25 mm found identical 35.4% rates of birth before 37 weeks with vaginal progesterone and control. 4
  5. FDA withdrew Makena and its generics in April 2023 after the required confirmatory trial failed to verify benefit; Makena was injectable 17-OHPC, not vaginal progesterone. 5

Is vaginal progesterone safe in each trimester?

  • First trimester. First-trimester progesterone used for fertility support is a different clinical question. The short-cervix evidence on this page begins with cervical-length assessment in the second trimester, not routine first-trimester self-use.
  • Second trimester. Second trimester is the key decision window. Current specialist guidance defines short cervix by standardized transvaginal measurement and recommends or considers vaginal progesterone before 24 weeks according to cervical length and history.
  • Third trimester. Third-trimester plans usually continue only to the prespecified stop point, membrane rupture, labor, or delivery. Starting after 24 weeks has much less certain evidence, so timing should come from the obstetric team.

Frequently asked questions

Who is a candidate for vaginal progesterone during pregnancy?

The strongest current indication is an asymptomatic singleton pregnancy with a short cervix measured by standardized transvaginal ultrasound before 24 weeks. Exact cervical-length thresholds, prior history, symptoms, dilation, and other findings determine the full obstetric plan.

Does vaginal progesterone actually lower the chance of an early birth?

Yes, for a defined short-cervix population. In one randomized trial of singleton pregnancies with a 10 to 20 mm cervix, birth before 33 weeks occurred in 8.9% with progesterone gel and 16.1% with placebo. That result does not apply to every pregnancy.

Is vaginal progesterone the same as the Makena shot?

No. Vaginal progesterone is placed in the vagina. Makena was an injectable synthetic progestin called 17-alpha hydroxyprogesterone caproate, or 17-OHPC. FDA withdrew Makena and its generics after confirmatory evidence did not verify benefit.

Does a prior spontaneous early birth alone justify vaginal progesterone?

Current ACOG guidance says vaginal progesterone should not be offered solely for a prior spontaneous early birth when the current singleton pregnancy does not have a shortened cervix. Serial transvaginal cervical-length assessment helps guide the discussion.

When is vaginal progesterone started and stopped?

Timing varies by formulation and protocol. In the randomized 90 mg gel trial, participants began the study medicine between 20 weeks 0 days and 23 weeks 6 days and continued to 36 weeks 6 days, membrane rupture, or delivery. A prescribed schedule should match the formulation and obstetric indication.

Is vaginal progesterone routinely used for twins?

No. The 2024 SMFM consult recommends against routine progesterone use for cervical shortening in twin gestations outside a clinical trial. Evidence and thresholds from singleton short-cervix studies should not be transferred to twins.

What side effects occurred in the short-cervix progesterone trial?

In the randomized gel trial, medication-related adverse events were not significantly different from placebo. Events reported in up to 2% included vaginal itching, discharge, candidiasis, and nausea. A single trial cannot exclude rare effects.

Can vaginal progesterone replace a cervical cerclage?

Vaginal progesterone and cerclage are not interchangeable for every patient. Cervical length, prior painless dilation or early birth, current dilation, and obstetric history determine which options are discussed. SMFM advises against cerclage for a 10 to 25 mm cervix without dilation in people with no prior spontaneous early birth.

Does vaginal progesterone help when a short cervix is first found after 24 weeks?

Evidence after 24 weeks is less certain than the mid-trimester evidence. A clinician should interpret when the cervix shortened, the measured length, symptoms, and prior history rather than starting vaginal progesterone from a late measurement without an obstetric plan.

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References

  1. Updated Clinical Guidance for the Use of Progestogen Supplementation for the Prevention of Recurrent Preterm Birth

    ACOG · https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2023/04/updated-guidance-use-of-progestogen-supplementation-for-prevention-of-recurrent-preterm-birth

  5. Makena (hydroxyprogesterone caproate injection) Information

    FDA · https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/makena-hydroxyprogesterone-caproate-injection-information

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.